PROJECT SUMMARY Over five million Americans have Alzheimer's disease (AD) or an AD-related dementia (AD/ADRD). These high- need, high-cost patients are vulnerable to receiving poor quality, uncoordinated care, ultimately leading to adverse health outcomes, poor quality of life, and misuse of resources. As recently concluded by the federally- funded Research Summit on Dementia Care, improving the care of PWD and their CGs is an urgent public health challenge that must be met and informed by high quality evidence. While prior research has elucidated opportunities to improve the care of PWD and their CGs, the adoption of promising interventions has been stymied by the lack of research evaluating their effectiveness when implemented under ?real-world? conditions. Pragmatic clinical trials embedded (ePCTs) in healthcare systems (HCS) have the potential to accelerate the translation of evidence-based interventions into clinical practice. Since its inception in 2012, the NIH Common Fund HCS Research Collaboratory has made pivotal contributions towards advancing the conduct of ePCTs. However, as concluded in a 2017 NIA-sponsored conference, ePCTs conducted with PWD and their CGs have unique considerations that merit specific focus. Thus, the overarching objective of this proposal is to build on the model of the NIH Collaboratory to establish the National Institute on Aging (NIA) AD/ADRD Research Collaboratory, co-led by the multiple principal investigators (MPIs), Drs. Vince Mor (Brown University) and Susan Mitchell (Hebrew SeniorLife (HSL)) and co-administered by their respective institutions. The Aims are: 1. To establish the infrastructure of the AD/ADRD Collaboratory, 2. To develop and disseminate guidelines for the conduct of all aspects of ePCTs among PWD and their CGs in partnership with HCS, 3. Enhance research development and investigator capacity to conduct ePCTs in PWD and their CGs within HCS, and 4. To disseminate knowledge and best practices to engage stakeholders in this research. Accomplished investigators from across the nation will lead the following Working Group Cores: 1. Technical and Data (B), J. Bynum, MD, MPH; 2. Regulation and Ethics (C), J. Karlawish, MD; 3. Design and Statistics (D), H. Allore, PhD; 4. Pilot Studies (E), A. Brody, PhD, RN; 5. Patient and CG Reported Outcomes (F), L. Hanson, MD, MPH; 6. Dissemination and Implementation (G), L. Gitlin, PhD/J. Gaugler, PhD; 7. HCS (H): E. Larson, MD, MPH, and Training (I): C. Callahan MD/A. Torke MD. An Administration Core (A) will integrate all critical functions across the Collaboratory. IMPACT: There is an urgent need to improve care provided by HCS for PWD and their CGs. ePCTs conducted are ideally-suited to test the effectiveness of interventions aimed at improving their health outcomes but require specific expertise, methodology, data sources, and industry partnerships. The knowledge, investigative experience, collaborations, and evidence generated by an AD/ADRD Collaboratory has the potential to transform the delivery, quality, and outcomes of care for Americans from all backgrounds with AD/ADRD and their CGs.